Two arms are better than one: parasite variation leads to combined inducible and constitutive innate immune responses

Parasites represent a major threat to all organisms which has led to the evolution of an array of complex and effective defence mechanisms. Common to both vertebrates and invertebrates are innate immune mechanisms that can be either constitutively expressed or induced on exposure to infection. In nature, we find that a combination of both induced and constitutive responses are employed by vertebrates, invertebrates and, to an extent, plants when they are exposed to a parasite. Here we use a simple within-host model motivated by the insect immune system, consisting of both constitutive and induced responses, to address the question of why both types of response are maintained so ubiquitously. Generally, induced responses are thought to be advantageous because they are only used when required but are too costly to maintain constantly, while constitutive responses are advantageous because they are always ready to act. However, using a simple cost function but with no a priori assumptions about relative costs, we show that variability in parasite growth rates selects for a strategy that combines both constitutive and induced defences. Differential costs are therefore not necessary to explain the adoption of both forms of defence. Clearly, hosts are likely to be challenged by variable parasites in nature and this is sufficient to explain why it is optimal to deploy both arms of the innate immune system.

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Commensal and Opportunistic Bacteria Present in the Microbiota in Atlantic Cod (Gadus morhua) Larvae Differentially Alter the Hosts’ Innate Immune Responses

Microorganisms ◽

10.3390/microorganisms10010024 ◽

2021 ◽

Vol 10 (1) ◽

pp. 24

Author(s):

Ragnhild Inderberg Vestrum ◽

Torunn Forberg ◽

Birgit Luef ◽

Ingrid Bakke ◽

Per Winge ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Atlantic Cod ◽

Innate Immune ◽

Rrna Gene ◽

Innate Immune Responses ◽

Transcriptional Responses ◽

Gut Morphology ◽

Germ Free ◽

Opportunistic Bacteria

The roles of host-associated bacteria have gained attention lately, and we now recognise that the microbiota is essential in processes such as digestion, development of the immune system and gut function. In this study, Atlantic cod larvae were reared under germ-free, gnotobiotic and conventional conditions. Water and fish microbiota were characterised by 16S rRNA gene analyses. The cod larvae’s transcriptional responses to the different microbial conditions were analysed by a custom Agilent 44 k oligo microarray. Gut development was assessed by transmission electron microscopy (TEM). Water and fish microbiota differed significantly in the conventional treatment and were dominated by different fast-growing bacteria. Our study indicates that components of the innate immune system of cod larvae are downregulated by the presence of non-pathogenic bacteria, and thus may be turned on by default in the early larval stages. We see indications of decreased nutrient uptake in the absence of bacteria. The bacteria also influence the gut morphology, reflected in shorter microvilli with higher density in the conventional larvae than in the germ-free larvae. The fact that the microbiota alters innate immune responses and gut morphology demonstrates its important role in marine larval development.

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Mitochondria surveillance systems trigger innate immune responses to bacterial pathogens via AMPK pathway in C. elegans

10.1101/2020.09.17.301036 ◽

2020 ◽

Author(s):

Shouyong Ju ◽

Hanqiao Chen ◽

Shaoying Wang ◽

Jian Lin ◽

Raffi V Aroian ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune ◽

Surveillance Systems ◽

Innate Immune Responses ◽

Energy Status ◽

Microbial Infection ◽

C Elegans ◽

Host Interaction ◽

Intracellular Energy

AbstractPathogen recognition and triggering pattern of host innate immune system is critical to understanding pathogen-host interaction. It is generally accepted that the microbial infection can be recognized by host via pattern-triggered immunity (PTI) or effector-triggered immunity (ETI) responses. Recently, non-PRR-mediated cellular surveillance systems have been reported as an important supplement strategy to PTI and ETI responses. However, the mechanism of how surveillance systems sense pathogens and trigger innate immune responses is largely unknown. In the present study, using Bacillus thuringiensis-Caenorhabditis elegans as a model, we found a new approach for surveillance systems to sense the pathogens through no-PPRs patterns. We reported C. elegans can monitor intracellular energy status through the mitochondrial surveillance system to triggered innate immune responses against pathogenic attack via AMP-activated protein kinase (AMPK). Consider that the mitochondria surveillance systems and AMPK are conserved components from worms to mammals, our study suggests that disrupting mitochondrial homeostasis to activate the immune system through AMPK-dependent pathways may widely existing in animals.

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The neuropeptide receptor NMUR-1 regulates the specificity of C. elegans innate immunity against pathogen infection

10.1101/2021.05.06.442992 ◽

2021 ◽

Author(s):

Phillip Wibisono ◽

Shawndra Wibisono ◽

Jan Watteyne ◽

Chia-Hui Chen ◽

Durai Sellegounder ◽

...

Keyword(s):

Innate Immunity ◽

Immune System ◽

Immune Responses ◽

Adaptive Immune System ◽

Innate Immune ◽

Innate Immune Responses ◽

Immune Genes ◽

C Elegans ◽

Adaptive Immune ◽

Functional Assays

A key question in current immunology is how the innate immune system generates high levels of specificity. Like most invertebrates, Caenorhabditis elegans does not have an adaptive immune system and relies solely on innate immunity to defend itself against pathogen attacks, yet it can still differentiate different pathogens and launch distinct innate immune responses. Here, we have found that functional loss of NMUR-1, a neuronal GPCR homologous to mammalian receptors for the neuropeptide neuromedin U, has diverse effects on C. elegans survival against various bacterial pathogens. Transcriptomic analyses and functional assays revealed that NMUR-1 modulates C. elegans transcription activity by regulating the expression of transcription factors, which, in turn, controls the expression of distinct immune genes in response to different pathogens. Our study has uncovered a molecular basis for the specificity of C. elegans innate immunity that could provide mechanistic insights into understanding the specificity of vertebrate innate immunity.

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Fasciola hepatica hijacks host macrophage miRNA machinery to modulate early innate immune responses

Scientific Reports ◽

10.1038/s41598-021-86125-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nham Tran ◽

Alison Ricafrente ◽

Joyce To ◽

Maria Lund ◽

Tania M. Marques ◽

...

Keyword(s):

Immune Responses ◽

Cell Function ◽

Fasciola Hepatica ◽

Innate Immune ◽

Innate Immune Responses ◽

Defence Mechanisms ◽

First Line ◽

M1 Macrophages ◽

Successful Infection ◽

Inflammatory Immune Response

AbstractFasciola hepatica, a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. Host macrophages, essential to the first-line defence mechanisms, are quickly restricted in their ability to initiate a classic protective pro-inflammatory immune response. We found that macrophages from infected animals are enriched with parasite-derived micro(mi)RNAs. The most abundant of these miRNAs, fhe-miR-125b, is released by the parasite via exosomes and is homologous to a mammalian miRNA, hsa-miR-125b, that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite fhe-miR-125b loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host miR-125b to negatively regulate the production of inflammatory cytokines. The hijacking of the miRNA machinery controlling innate cell function could be a fundamental mechanism by which worm parasites disarm the early immune responses of their host to ensure successful infection.

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The innate immune system

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0038 ◽

2020 ◽

pp. 307-314

Author(s):

Paul Bowness

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Cell Types ◽

Innate Immune ◽

Microbial Pathogens ◽

Innate Immune Responses ◽

Adaptive Immune ◽

System P ◽

Different Cell Types

The innate immune system comprises evolutionarily ancient mechanisms that mediate first-line responses against microbial pathogens, and are also important in priming and execution of adaptive immune responses, and in defence against tumours. These responses, which recognize microbial non-self, damaged self, and absent self, are characterized by rapidity of action and they involve various different cell types, cell-associated receptors, and soluble factors. Previously thought to lack plasticity or memory, certain innate immune responses have recently been shown to be capable of ‘learning’ or ‘training’. Most cells of the innate immune system are derived from the myeloid precursors in the bone marrow. These include monocytes and their derivatives—macrophages and dendritic cells, blood granulocytes (neutrophils, basophils, and eosinophils), and tissue mast cells.

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lncRNAs Regulate Innate Immune Responses and Their Roles in Macrophage Polarization

Mediators of Inflammation ◽

10.1155/2018/8050956 ◽

2018 ◽

Vol 2018 ◽

pp. 1-8 ◽

Cited By ~ 13

Author(s):

Zhen Wang ◽

Ying Zheng

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Macrophage Polarization ◽

Noncoding Rnas ◽

Innate Immune ◽

Microbial Pathogens ◽

Innate Immune Responses ◽

First Line ◽

New Class

The innate immune system is the first line of defense against microbial pathogens. The activated innate immune system plays important roles in eliciting antimicrobial defenses. Despite the benefits of innate immune responses, excessive inflammation will cause host damage. Thus, tight regulation of these processes is required for the maintenance of immune homeostasis. Recently, a new class of long noncoding RNAs (lncRNAs) has emerged as important regulators in many physiological and pathological processes. Dysregulated lncRNAs have been found to be associated with excessive or uncontrolled inflammation. In this brief review, we summarize the roles of functional lncRNAs in regulating innate immune responses. We also discuss the roles of lncRNAs in macrophage polarization, an important molecular event in the innate immune responses.

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Coordinate actions of innate immune responses oppose those of the adaptive immune system duringSalmonellainfection of mice

Science Signaling ◽

10.1126/scisignal.aaa9303 ◽

2016 ◽

Vol 9 (410) ◽

pp. ra4-ra4 ◽

Cited By ~ 13

Author(s):

Andrew N. Hotson ◽

Smita Gopinath ◽

Monica Nicolau ◽

Anna Khasanova ◽

Rachel Finck ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Adaptive Immune System ◽

Innate Immune ◽

Innate Immune Responses ◽

Adaptive Immune

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Rapid Virus Dissemination in Infant Macaques after Oral Simian Immunodeficiency Virus Exposure in the Presence of Local Innate Immune Responses

Journal of Virology ◽

10.1128/jvi.02240-05 ◽

2006 ◽

Vol 80 (13) ◽

pp. 6357-6367 ◽

Cited By ~ 43

Author(s):

Kristina Abel ◽

Bapi Pahar ◽

Koen K. A. Van Rompay ◽

Linda Fritts ◽

Clarissa Sin ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Simian Immunodeficiency Virus ◽

Virus Replication ◽

Proinflammatory Cytokines ◽

Innate Immune ◽

Lymphoid Tissues ◽

Innate Immune Responses ◽

Virus Dissemination ◽

Immunodeficiency Virus

ABSTRACT A vaccine to protect human immunodeficiency virus (HIV)-exposed infants is an important goal in the global fight against the HIV pandemic. Two major challenges in pediatric HIV vaccine design are the competence of the neonatal/infant immune system in comparison to the adult immune system and the frequent exposure to HIV via breast-feeding. Based on the hypothesis that an effective vaccine needs to elicit antiviral immune responses directly at the site of virus entry, the pattern of virus dissemination in relation to host immune responses was determined in mucosal and lymphoid tissues of infant macaques at 1 week after multiple oral exposures to simian immunodeficiency virus (SIV). The results show that SIV disseminates systemically by 1 week. Infant macaques can respond rapidly to virus challenge and mount strong innate immune responses. However, despite systemic infection, these responses are most pronounced in tissues close to the viral entry site, with the tonsil being the primary site of virus replication and induction of immune responses. Thus, distinct anatomic compartments are characterized by unique cytokine gene expression patterns. Importantly, the early response at mucosal entry sites is dominated by the induction of proinflammatory cytokines, while cytokines with direct antiviral activity, alpha/beta interferons, are only minimally induced. In contrast, both antiviral and proinflammatory cytokines are induced in lymphoid tissues. Thus, although infant macaques can respond quickly to oral viral challenge, the locally elicited immune responses at mucosal entry sites are likely to favor immune activation and thereby virus replication and are insufficient to limit virus replication and dissemination.

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Nanoparticles induce dermal and intestinal innate immune system responses in zebrafish embryos

Environmental Science Nano ◽

10.1039/c8en00002f ◽

2018 ◽

Vol 5 (4) ◽

pp. 904-916 ◽

Cited By ~ 20

Author(s):

Nadja R. Brun ◽

Bjørn E. V. Koch ◽

Mónica Varela ◽

Willie J. G. M. Peijnenburg ◽

Herman P. Spaink ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Innate Immune System ◽

Innate Immune ◽

Zebrafish Embryos ◽

Innate Immune Responses

Metal and plastic nanoparticles elicit innate immune responses in the skin and intestine of zebrafish embryos potentially serving as key event for AOPs.

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A Secreted Bacterial Peptidylarginine Deiminase Can Neutralize Human Innate Immune Defenses

mBio ◽

10.1128/mbio.01704-18 ◽

2018 ◽

Vol 9 (5) ◽

Cited By ~ 22

Author(s):

Tim Stobernack ◽

Marines du Teil Espina ◽

Lianne M. Mulder ◽

Laura M. Palma Medina ◽

Dillon R. Piebenga ◽

...

Keyword(s):

Immune System ◽

Immune Responses ◽

Immune Evasion ◽

Histone H3 ◽

Innate Immune ◽

Innate Immune Responses ◽

Peptidylarginine Deiminase ◽

Oral Pathogen ◽

Content Type ◽

Immune Defenses

ABSTRACTThe keystone oral pathogenPorphyromonas gingivalisis associated with severe periodontitis. Intriguingly, this bacterium is known to secrete large amounts of an enzyme that converts peptidylarginine into citrulline residues. The present study was aimed at identifying possible functions of this citrullinating enzyme, namedPorphyromonaspeptidylarginine deiminase (PPAD), in the periodontal environment. The results show that PPAD is detectable in the gingiva of patients with periodontitis, and that it literally neutralizes human innate immune defenses at three distinct levels, namely bacterial phagocytosis, capture in neutrophil extracellular traps (NETs), and killing by the lysozyme-derived cationic antimicrobial peptide LP9. As shown by mass spectrometry, exposure of neutrophils to PPAD-proficient bacteria reduces the levels of neutrophil proteins involved in phagocytosis and the bactericidal histone H2. Further, PPAD is shown to citrullinate the histone H3, thereby facilitating the bacterial escape from NETs. Last, PPAD is shown to citrullinate LP9, thereby restricting its antimicrobial activity. The importance of PPAD for immune evasion is corroborated in the infection modelGalleria mellonella, which only possesses an innate immune system. Together, the present observations show that PPAD-catalyzed protein citrullination defuses innate immune responses in the oral cavity, and that the citrullinating enzyme ofP. gingivalisrepresents a new type of bacterial immune evasion factor.IMPORTANCEBacterial pathogens do not only succeed in breaking the barriers that protect humans from infection, but they also manage to evade insults from the human immune system. The importance of the present study resides in the fact that protein citrullination is shown to represent a new bacterial mechanism for immune evasion. In particular, the oral pathogenP. gingivalisemploys this mechanism to defuse innate immune responses by secreting a protein-citrullinating enzyme. Of note, this finding impacts not only the global health problem of periodontitis, but it also extends to the prevalent autoimmune disease rheumatoid arthritis, which has been strongly associated with periodontitis, PPAD activity, and loss of tolerance against citrullinated proteins, such as the histone H3.

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